Abstract
microRNAs (miRNAs) are highly conserved, small non-coding RNAs that regulate gene expression at the posttranscriptional level. They have crucial roles in organismal development, homeostasis, and cellular responses to pathological stress. The lymphatic system is a large vascular network that actively regulates the immune response through antigen trafficking, cytokine secretion, and inducing peripheral tolerance. Here, we review the role of miRNAs in the lymphatic endothelium with a particular focus on their role in lymphatic endothelial cell (LEC) plasticity, inflammation, and regulatory function. We highlight the lineage plasticity of LECs during inflammation and the importance of understanding the regulatory role of miRNAs in these processes. We propose that targeting miRNA expression in lymphatic endothelium can be a novel strategy in treating human pathologies associated with lymphatic dysfunction.
Highlights
The lymphatic system is a transport network that regulates tissue fluid homeostasis, the absorption of macromolecules, and the trafficking of immune cells [1]
lymphatic vessel hyaluronan receptor-1 (LYVE-1) is a widely used lymphatic-specific marker, implicated in cellular trafficking and a homolog of the CD44 glycoprotein [12, 13]. Both vascular endothelial growth factor receptor-3 (VEGFR-3) and LYVE-1 are expressed during early endothelial cell development and become restricted to lymphatic endothelial cell (LEC) at later stages
MiR-1236 is lowly expressed in human LECs, it may be upregulated during inflammation-induced lymphangiogenesis to control the expression of VEGF-C/VEGFR-3 signaling
Summary
The lymphatic system is a transport network that regulates tissue fluid homeostasis, the absorption of macromolecules, and the trafficking of immune cells [1]. In addition to transcriptional regulation, posttranscriptional mechanisms play a key role in LEC responses to inflammation. MiRNA-MEDIATED SILENCING microRNAs are a class of highly conserved, small non-coding RNA (~20–24 nt) that regulate gene expression at the posttranscriptional level of all biological pathways including cell development, differentiation, and function [2]. Binding sites are generally 8mers or canonical sites that enable high miRNA regulation of mRNA expression [6]. Due to this short target sequence, miRNAs can have multiple targets, and it is predicted that 30% of all protein-coding genes is under miRNA regulation in mammals [7]
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